الفهرس 
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Abstract
The present study was performed on one hundred and thirty five persons. Seventy five are T2DM patients and sixty persons are apparently healthy used as controls. Diabetic patients were classified into two groups according to A/ C ratio, group I: twenty five patients were normoalbuminuric (A/C ratio < 30 mg/g), group II (DN group): fifty patients complained of DN, group IIa: twenty five patients were microalbuminuric (A/C ratio 30 to < 300 mg/g) and group IIb: twenty five patients were macroalbuminuric (A/C ratio > 300 mg/g).
The aim of this work was to find whether polymorphisms of MTHFR C677T (rs1801133) and A1298C (rs1801133) are risk factors for DN among T2DM patients or not.
The results of this study revealed that BMI was significantly increased in diabetic patients when compared to controls and in DN patients when compared to normoalbuminuric patients.
The duration of diabetes was significant increase in DN patients when compared to normoalbuminuric patients. Also, there was a significant increase in the tendency to use insulin as a treatment of diabetes in DN group when compared to normoalbuminuric patients. In addition, the frequency of diabetic retinopathy and coronary heart diseases significantly increased in DN patients when compared to normoalbuminuric patients.
On the other hand, haemoglobin, serum total protein and serum albumin showed significant decrease in diabetic patients when compared to controls and in DN patients when compared to normoalbuminuric patients.
Lipid profile in this study showed that triglycerides, Cholesterol, LDL-C and VLDL-C significantly increased in diabetic patients when compared to controls and in DN patients when compared to normoalbuminuric patients while HDL-C was significantly decreased in diabetic patients when compared to controls and in DN patients when compared to normoalbuminuric patients.
Among the study participants, fasting blood glucose level and HbA1c level were significantly increased in diabetic patients when compared to controls and in DN patients when compared to normoalbuminuric patients.
Kidney function tests of the studied population showed that serum creatinine, urea, uric acid levels significantly increased in diabetic patients when compared to controls, and in DN patients when compared to normoalbuminuric patients, while (eGFR) showed significant decrease in diabetic patients when compared to controls and in DN compared to normoalbuminuric patients.
Urine examination of the studied population showed significant increase in albuminuria, pyuria and hematuria in diabetic patients when compared to controls and in DN patients when compared to normoalbuminuric patients while a significant decrease in specific gravity in DN when compared to normoalbuminuric patients.
In the present study, the presence of (rs1801133) mutant genotypes (CT+TT) or the mutant T allele significantly increased in diabetic patients when compared to controls and in DN patients when compared to normoalbuminuric patients.
The presence of mutant genotypes (AC+CC) of (rs1801131) showed no significant difference in diabetic patients when compared to controls and in DN patients when compared to normoalbuminuric patients while the presence of mutant C allele significantly increase in diabetic patients when compared to controls but not significantly differ in DN patients and normoalbuminuric patients.
The haplotypes CT of (rs1801133) / CC of (rs1801131) and TT of (rs1801133) / AC of ( rs1801131) were found in patients with nephropathy while absent in normoalbuminuric diabetic patients, these haplotypes may be considered as risk factor for nephropathy.
The presence of T allele of (rs1801133) and absence of C allele of (rs1801131) increase risk of nephropathy while the presence of both mutant alleles T allele of (rs1801133) and C allele of (rs1801131) markedly increase the risk of nephropathy.
Conclusion
MTHFR C677T(rs1801133) polymorphism was a risk factor for development of type 2 diabetes and diabetic nephropathy in type 2 Egyptian diabetic patients while MTHFR A1298C (rs1801131) was not a risk factor. The presence of polymorphism in the two genes synergistically acts to increase risk of diabetic nephropathy.
Recommendations
-Serum homocystiene level should be estimated as the (rs1801133) and (rs1801131) were associated with hyperhomocystienemia and harmful effects were mostly due to hyperhomocystienemia.
-Studying the association (rs1801133) and (rs1801131) polymorphism with the risk of other diseases e.g. coronary heart disease, retinopathy, glaucoma and risk of cancer e.g. leukemia, gastric and colorectal cancer, breast cancer… etc
-Supplementation of folic acid and vitamin B12 to diabetic patients as the effect of MTHFR gene polymorphism increase in the presence of deficiency of folic acid and vitamin of B12.
- Further studies in larger numbers of patients are necessary to establish a role of MTHFR polymorphism in the series of DN.
-Multicentric study should be performed that will help in increasing the statistical power by alleviating possible differences of studied subjects, as the ethnic background, gene–environment interaction including economic and nutritional status, as well as differences in the stage of nephropathy, and the duration of diabetes.
-Future studying of rs1801133 and rs1801131 polymorphisms could be done together with other genes associated with development of diabetic nephropathy e.g. ACE receptor gene.
-Using DNA Sequencing technique for detection of different MTHFR gene polymorphisms will increase accuracy of the results.